Abstract

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts.Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6-59 mo) by country and infection-burden category.Design: Cross-sectional data from 16 surveys (n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group.Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high-infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high-infection categories, respectively.Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs.

Venn diagrams illustrating the prevalence of iron deficiency, anemia, iron deficiency and anemia, and proportion of anemic individuals with iron deficiency in preschool children by category of infection burden: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Values are proportions. Iron deficiency was defined as an inflammation-adjusted ferritin concentration <12 μg/L. Ferritin values were adjusted by regression with the use of reference CRP and AGP concentrations that were equivalent to the first decile of a reference population. Values were adjusted for CRP and AGP when both were available or for only CRP or AGP if only one was available. Any inflammation defined as was defined as a CRP concentration >5 mg/L or AGP concentration >1 g/L. Only AGP data were available in Nicaragua and Pakistan. Only CRP data were available in Colombia, Georgia, Mexico (2006 and 2012), and the United States. Anemia was defined as a hemoglobin concentration <110 g/L. Countries were grouped as follows—low infection burden: Georgia and the United States; moderate infection burden: Colombia, Mexico (2006 and 2012), and Nicaragua; high infection burden: Bangladesh, Laos, Pakistan, Papua New Guinea, and the Philippines; and very high infection burden: Cameroon, Côte d’Ivoire, Kenya (2007 and 2010), and Liberia. AGP, α-1-acid glycoprotein; CRP, C-reactive protein.

Prevalence (95% CI) of anemia in children with and without iron deficiency by category of infectious disease burden and adjustment of an iron-status indicator (ferritin) for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Ferritin values were adjusted by regression with the use of reference CRP and AGP concentrations that were equivalent to the first decile of a reference population. Values were adjusted for CRP and AGP when both were available or for only CRP or AGP if only one was available. Countries were grouped as follows—low infection burden: Georgia and the United States; moderate infection burden: Colombia, Mexico (2006 and 2012), and Nicaragua; high infection burden: Bangladesh, Laos, Pakistan, Papua New Guinea, and the Philippines; and very high infection burden: Cameroon, Côte d’Ivoire, Kenya (2007 and 2010), and Liberia. AGP, α-1-acid glycoprotein; CRP, C-reactive protein; Hb, hemoglobin.